全文获取类型
收费全文 | 1258篇 |
免费 | 141篇 |
专业分类
1399篇 |
出版年
2023年 | 10篇 |
2022年 | 27篇 |
2021年 | 41篇 |
2020年 | 27篇 |
2019年 | 31篇 |
2018年 | 27篇 |
2017年 | 39篇 |
2016年 | 50篇 |
2015年 | 68篇 |
2014年 | 80篇 |
2013年 | 104篇 |
2012年 | 119篇 |
2011年 | 107篇 |
2010年 | 58篇 |
2009年 | 48篇 |
2008年 | 88篇 |
2007年 | 67篇 |
2006年 | 68篇 |
2005年 | 59篇 |
2004年 | 61篇 |
2003年 | 47篇 |
2002年 | 60篇 |
2001年 | 10篇 |
2000年 | 6篇 |
1999年 | 15篇 |
1998年 | 10篇 |
1997年 | 9篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1969年 | 2篇 |
1952年 | 1篇 |
排序方式: 共有1399条查询结果,搜索用时 0 毫秒
91.
Questions: How can one explicitly quantify, and separately measure, stress and disturbance gradients? How do these gradients affect functional composition in early successional plant communities and to what extent? Can we accurately predict trait composition from knowledge of these gradients? Location: Southern Quebec, Canada. Methods: Using eight environmental variables measured in 48 early successional plant communities, we estimated stress and disturbance gradients through structural equation modelling. We then measured 10 functional traits on the most abundant species of these 48 communities and calculated their community‐level mean and variance weighted by the relative abundance of each species. Finally, we related these community‐weighted means and variances to the estimated stress and disturbance gradients using general linear models or generalized additive models. Results: We obtained a well‐fitting measurement model of the stress and disturbance gradients existing in our sites. Of the 10 studied traits, only average plant reproductive height was strongly correlated with the stress (r2=0.464) and disturbance (r2=0.543) gradients. Leaf traits were not significantly related to either the stress or disturbance gradients. Conclusions: The well‐fitting measurement model of the stress and disturbance gradients, combined with the generally weak trait–environment linkages, suggests that community assembly in these early successional plant communities is driven primarily by stochastic processes linked to the history of arrival of propagules and not to trait‐based environmental filtering. 相似文献
92.
93.
Errors occur randomly and at low frequency during the translation of mRNA. However, such errors may also be programmed by the sequence and structure of the mRNA. These programmed events are called 'recoding' and are found mostly in viruses, in which they are usually essential for viral replication. Translational errors at a stop codon may also be induced by drugs, raising the possibility of developing new treatment protocols for genetic diseases on the basis of nonsense mutations. Many studies have been carried out, but the molecular mechanisms governing these events remain largely unknown. Studies on the yeast Saccharomyces cerevisiae have contributed to characterization of the HIV-1 frameshifting site and have demonstrated that frameshifting is conserved from yeast to humans. Yeast has also proved a particularly useful model organism for deciphering the mechanisms of translation termination in eukaryotes and identifying the factors required to obtain a high level of natural suppression. These findings open up new possibilities for large-scale screening in yeast to identify new drugs for blocking HIV replication by inhibiting frameshifting or restoring production of the full-length protein from a gene inactivated by a premature termination codon. We explore these two aspects of the contribution of yeast studies to human medicine in this review. 相似文献
94.
Cécile Frolet Meryam Beniazza Laure Roux Benoit Gallet Marjolaine Noirclerc-Savoye Thierry Vernet Anne Marie Di Guilmi 《BMC microbiology》2010,10(1):190
Background
Streptococcus pneumoniae is a widely distributed commensal Gram-positive bacteria of the upper respiratory tract. Pneumococcal colonization can progress to invasive disease, and thus become lethal, reason why antibiotics and vaccines are designed to limit the dramatic effects of the bacteria in such cases. As a consequence, pneumococcus has developed efficient antibiotic resistance, and the use of vaccines covering a limited number of serotypes such as Pneumovax® and Prevnar® results in the expansion of non-covered serotypes. Pneumococcal surface proteins represent challenging candidates for the development of new therapeutic targets against the bacteria. Despite the number of described virulence factors, we believe that the majority of them remain to be characterized. This is the reason why pneumococcus invasion processes are still largely unknown.Results
Availability of genome sequences facilitated the identification of pneumococcal surface proteins bearing characteristic motifs such as choline-binding proteins (Cbp) and peptidoglycan binding (LPXTG) proteins. We designed a medium throughput approach to systematically test for interactions between these pneumococcal surface proteins and host proteins (extracellular matrix proteins, circulating proteins or immunity related proteins). We cloned, expressed and purified 28 pneumococcal surface proteins. Interactions were tested in a solid phase assay, which led to the identification of 23 protein-protein interactions among which 20 are new.Conclusions
We conclude that whether peptidoglycan binding proteins do not appear to be major adhesins, most of the choline-binding proteins interact with host proteins (elastin and C reactive proteins are the major Cbp partners). These newly identified interactions open the way to a better understanding of host-pneumococcal interactions.95.
Ecological systems can show complex and sometimes abrupt responses to environmental change, with important implications for their resilience. Theories of alternate stable states have been used to predict regime shifts of ecosystems as equilibrium responses to sufficiently slow environmental change. The actual rate of environmental change is a key factor affecting the response, yet we are still lacking a non-equilibrium theory that explicitly considers the influence of this rate of environmental change. We present a metacommunity model of predator–prey interactions displaying multiple stable states, and we impose an explicit rate of environmental change in habitat quality (carrying capacity) and connectivity (dispersal rate). We study how regime shifts depend on the rate of environmental change and compare the outcome with a stability analysis in the corresponding constant environment. Our results reveal that in a changing environment, the community can track states that are unstable in the constant environment. This tracking can lead to regime shifts, including local extinctions, that are not predicted by alternative stable state theory. In our metacommunity, tracking unstable states also controls the maintenance of spatial heterogeneity and spatial synchrony. Tracking unstable states can also lead to regime shifts that may be reversible or irreversible. Our study extends current regime shift theories to integrate rate-dependent responses to environmental change. It reveals the key role of unstable states for predicting transient dynamics and long-term resilience of ecological systems to climate change. 相似文献
96.
Catherine Hermant Antoine Boivin Laure Teysset Valérie Delmarre Amna Asif-Laidin Marius van den Beek Christophe Antoniewski Stéphane Ronsseray 《Genetics》2015,201(4):1381-1396
Transposable element activity is repressed in the germline in animals by PIWI-interacting RNAs (piRNAs), a class of small RNAs produced by genomic loci mostly composed of TE sequences. The mechanism of induction of piRNA production by these loci is still enigmatic. We have shown that, in Drosophila melanogaster, a cluster of tandemly repeated P-lacZ-white transgenes can be activated for piRNA production by maternal inheritance of a cytoplasm containing homologous piRNAs. This activated state is stably transmitted over generations and allows trans-silencing of a homologous transgenic target in the female germline. Such an epigenetic conversion displays the functional characteristics of a paramutation, i.e., a heritable epigenetic modification of one allele by the other. We report here that piRNA production and trans-silencing capacities of the paramutated cluster depend on the function of the rhino, cutoff, and zucchini genes involved in primary piRNA biogenesis in the germline, as well as on that of the aubergine gene implicated in the ping-pong piRNA amplification step. The 21-nt RNAs, which are produced by the paramutated cluster, in addition to 23- to 28-nt piRNAs are not necessary for paramutation to occur. Production of these 21-nt RNAs requires Dicer-2 but also all the piRNA genes tested. Moreover, cytoplasmic transmission of piRNAs homologous to only a subregion of the transgenic locus can generate a strong paramutated locus that produces piRNAs along the whole length of the transgenes. Finally, we observed that maternally inherited transgenic small RNAs can also impact transgene expression in the soma. In conclusion, paramutation involves both nuclear (Rhino, Cutoff) and cytoplasmic (Aubergine, Zucchini) actors of the piRNA pathway. In addition, since it is observed between nonfully homologous loci located on different chromosomes, paramutation may play a crucial role in epigenome shaping in Drosophila natural populations. 相似文献
97.
Quinternet M Tsan P Selme L Beaufils C Jacob C Boschi-Muller S Averlant-Petit MC Branlant G Cung MT 《Biochemistry》2008,47(48):12710-12720
The DsbD protein is essential for electron transfer from the cytoplasm to the periplasm of Gram-negative bacteria. Its N-terminal domain dispatches electrons coming from cytoplasmic thioredoxin (Trx), via its central transmembrane and C-terminal domains, to its periplasmic partners: DsbC, DsbE/CcmG, and DsbG. Previous structural studies described the latter proteins as Trx-like folds possessing a characteristic C-X-X-C motif able to generate a disulfide bond upon oxidation. The Escherichia coli nDsbD displays an immunoglobulin-like fold in which two cysteine residues (Cys103 and Cys109) allow a disulfide bond exchange with its biological partners.We have determined the structure in solution and the backbone dynamics of the C103S mutant of the N-terminal domain of DsbD from Neisseria meningitidis. Our results highlight significant structural changes concerning the beta-sheets and the local topology of the active site compared with the oxidized form of the E. coli nDsbD. The structure reveals a "cap loop" covering the active site, similar to the oxidized E. coli nDsbD X-ray structure. However, regions featuring enhanced mobility were observed both near to and distant from the active site, revealing a capacity of structural adjustments in the active site and in putative interaction areas with nDsbD biological partners. Results are discussed in terms of functional consequences. 相似文献
98.
Regulation of translation via stop codon readthrough (SC-RT) expands not only tissue-specific but also viral proteomes in humans and, therefore, represents an important subject of study. Understanding this mechanism and all involved players is critical also from a point of view of prospective medical therapies of hereditary diseases caused by a premature termination codon. tRNAs were considered for a long time to be just passive players delivering amino acid residues according to the genetic code to ribosomes without any active regulatory roles. In contrast, our recent yeast work identified several endogenous tRNAs implicated in the regulation of SC-RT. Swiftly emerging studies of human tRNA-ome also advocate that tRNAs have unprecedented regulatory potential. Here, we developed a universal U6 promotor-based system expressing various human endogenous tRNA iso-decoders to study consequences of their increased dosage on SC-RT employing various reporter systems in vivo. This system combined with siRNA-mediated downregulations of selected aminoacyl-tRNA synthetases demonstrated that changing levels of human tryptophan and tyrosine tRNAs do modulate efficiency of SC-RT. Overall, our results suggest that tissue-to-tissue specific levels of selected near-cognate tRNAs may have a vital potential to fine-tune the final landscape of the human proteome, as well as that of its viral pathogens. 相似文献
99.
Hamdi Jaafar Majdi Rouis Laure Coudrat Thierry Gélat Timothy David Noakes Tarak Driss 《PloS one》2015,10(8)
The aim of this study was to examine the impact of emotional eliciting pictures on neuromuscular performance during repetitive supramaximal cycling exercises (RSE). In a randomized order, twelve male participants were asked to perform five 6-s cycle sprints (interspaced by 24 s of recovery) on a cycle ergometer in front of neutral, pleasant or unpleasant pictures. During each RSE, mean power output (MPO) and electromyographic activity [root mean square (RMS) and median frequency (MF)] of the vastus lateralis and vastus medialis muscles were analyzed. Neuromuscular efficiency (NME) was calculated as the ratio of MPO to RMS. Higher RMS (232.17 ± 1.17 vs. 201.90 ± 0.47 μV) and MF (68.56 ± 1.78 vs. 64.18 ± 2.17 Hz) were obtained in pleasant compared to unpleasant conditions (p < 0.05). This emotional effect persisted from the first to the last sprint. Higher MPO was obtained in pleasant than in unpleasant conditions (690.65 ± 38.23 vs. 656.73 ± 35.95 W, p < 0.05). However, this emotional effect on MPO was observed only for the two first sprints. NME decreased from the third sprint (p < 0.05), which indicated the occurrence of peripheral fatigue after the two first sprints. These results suggested that, compared with unpleasant pictures, pleasant ones increased the neuromuscular performance during RSE. Moreover, the disappearance of the beneficial effect of pleasant emotion on mechanical output from the third sprint appears to be due to peripheral fatigue. 相似文献
100.